3H-Nitrendipine, a Ca2+-channel antagonist, was used as a biochemical tool to isolate an endogenous ligand that modulates Ca2+ channel activity. Brain extracts contain a low molecular weight material (2000 d) that displaces 3H-nitrendipine in a noncompetitive fashion, decreases voltage-dependent and glutamate receptor-dependent 45Ca2+ uptake in cerebellar granule cells and decreases voltage-dependent Ca2+ channel activity in patch clamped cardiac cells.